Secondary metabolites interactions with proteins

Whereas many secondary metabolites interact with multiple targets, and thus have unspecific broad (pleiotropic) activities, others, especially alkaloids, are more specific and interact exclusively with a single particular target. Secondary metabolites with broad and nonspecific activities interact mainly with proteins, biomembranes, and DNA/RNA which are present in all organisms. 

The nature of plants having secondary metabolites as defensive agents greatly increases the expectation that there will be interactions with other botanical products and drugs. If well-established traditional botanical products are used according to directions, they are likely a low risk. Risk increases when botanical products are combined with conventional drug therapies and lies in the possibility of unknown natural product-drug interactions. Other risks include product deviation due to misidentification of species, the lack of standardization, or adulteration. Most of the interactions have been reported with cytochrome P-450 (CYP) 3A4, but there are interactions with other metabolism enzymes and transport proteins. 

There are numerous examples of the inhibition of biosynthesis by fungicides. Some fungicidal secondary metabolites, like cyclohexi-mide and blasticidine, interfere with synthesis of peptide bonds at the ribosomal site (2). Another, kasugamycine, influences aminoacyl-t-RNA/ribosome interactions (3). Finally, another mechanism inhibiting protein biosynthesis is realized on the DNA/RNA- level by the... 

Aptamers, as biosensors, find many applications. Possible aptamer ligands are proteins, other biological macromolecules, as well as the biological context in which these occur (i.e., viruses, bacteria, and eukaryotic cells). Aptamers can interact with small molecules such as metal ions and drugs, as well as primary and secondary metabolites (amino acids, nucleotides, sugars, peptides). 

Looking at secondary metabolites from a biological perspective, their chemical diversity is the result of their diverse biological purposes, i.e. the requirement to interact with a large variety of target proteins. It is not surprising, therefore, that natural compounds can directly represent drug candidates without further modification. 

The existence of secondary metabolites that may fortuitously bind to proteins in the human body may also be illustrated in the nutrition field. Some recent research has investigated plant estrogens, molecules that may have hormonal activity in humans, despite the fact that they have no similar role in the plant. Thus, chance interactions of external molecules with human proteins is a major topic of consideration in all of biological sciences. 

Identification of proteins interacting with the promotor region of the secondary metabolite biosynthetic gene cluster... 

A new secondary metabolite, 8-0-methylsclerotiorinamine (27), was isolated from a strain of Penicillium multicolor, and its structure was established using NMR spectroscopy and chemical evidence. The metabolite significantly inhibited the binding between the Grb2-SH2 domain and the phosphopeptide derived from the She protein and also blocked the protein-protein interactions of Grb2-Shc in cell-based experiments, with IC50 values of 5.3 and 50 pM, respectively [85]. 

The different classes of secondary metabolites are made from compounds originating in the primary metabolism (Fig 3.21). To make a secondary metabolite a special metabolic pathway for its synthesis is needed. Often all the enzymes needed plus regulatory proteins and export proteins are clustered at the same location of the genome. The secondary metabolites where once regarded as some kind of surplus metabolism not needed in nature but rather a consequence of growing in rich laboratory media. Today they are considered as important compounds used in the interactions with other organisms or the environment and not secondary to fungal survival in nature at all. 

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